This phase 2 study examined the efficacy and safety of tolvaptan, an aquaretic drug, in the treatment of ascites associated with cancer.
In the dose-escalation phase, oral tolvaptan was initiated at a dose of 3.75mg/day, and the dose was increased daily to 7.5, 15 and 30mg/day. Dose escalation was terminated once the increase from baseline in the daily urine volume reached 500ml, at which point the patient proceeded to the maintenance phase of 5-7days. Improvement of ascites was determined primarily by reduction in body weight and ascitic fluid volume.
The mean change from baseline in body weight was maintained below 0kg throughout the study. The mean change (±standard deviation) from baseline in ascitic fluid volume at the end of treatment (EOT) was 237.45±868.14ml in 33 evaluable patients. Although an increase from baseline in ascitic fluid volume at the EOT was observed in 23 of 33 patients (maximum 1589.3ml, minimum 3.83ml), a reduction in ascitic fluid volume was observed in the remaining 10 patients (maximum -2304.3ml, minimum -27.5ml). The common treatment-emergent adverse events included vomiting (5 of 43 patients, 11.6%), abdominal distension, constipation, thirst, blood osmolarity increased and renal impairment (3 of 43 patients, 7.0% each).
Tolvaptan seemed to have no definitive effect on reducing ascites; however, it might be effective in at least some cancer patients. No new safety concerns were identified at doses of 3.75-30mg/day.
Tolvaptan seemed to have no definitive effect on reducing ascites; however, it might be effective in at least some cancer patients. No new safety concerns were identified at doses of 3.75-30 mg/day.Despite the burden of varicella, there is no universal varicella vaccination (UVV) programme in the United Kingdom (UK) due to concerns this could increase herpes zoster (HZ) incidence. This study assessed the cost-utility of a first-dose monovalent (V) or quadrivalent (MMRV) followed by a second-dose quadrivalent (MMRV) UVV programmes. GSK and MSD varicella-containing vaccines (VCVs) were considered.
A dynamic transmission and cost-effectiveness models were adapted to the UK. Outcomes measured included varicella and HZ incidences, the incremental cost-utility ratio (ICURs) over a lifetime horizon. The payer and societal perspectives were evaluated.
The impact of V-MMRV and MMRV-MMRV UVV programmes on varicella incidence was comparable between both VCVs at equilibrium. HZ incidence increased by 1.6%-1.7% over seven years after UVV start, regardless of the strategies, then decreased by &gt;95% at equilibrium. ICURs ranged from £5,665 (100 years) to £18,513 (20 years) per quality-adjusted life year (QALY) gained with V-MMRV; and from £9,220 to £27,101 per QALY gained with MMRV-MMRV (payer perspective). MMRV-MMRV was cost-effective in medium- and long-terms with GSK VCV, and only cost-effective at long-term with MSD VCV at £20,000 per QALY gained threshold. Without the exogenous boosting hypothesis, HZ incidence decreased through UVV implementation. ICURs were most sensitive to discount rates and MMRV price.
A 2-dose UVV was demonstrated to be a cost-effective alternative to no vaccination. With comparable effectiveness as MSD VCV at lower costs, GSK VCV may offer higher value for money.
A 2-dose UVV was demonstrated to be a cost-effective alternative to no vaccination. With comparable effectiveness as MSD VCV at lower costs, GSK VCV may offer higher value for money.HPV attributable oropharyngeal cancer (HPV-OPC) incidence is increasing in many high-income countries among men. Factors associated with oral HPV persistence, the precursor of HPV-OPC, is unknown. Data from the HPV Infection in Men (HIM) study which followed participants &gt;7 years were utilized to examine rates of persistence and associated factors.
Oral gargle samples from 3095 HIM study participants were HPV genotyped using SPF10 PCR-DEIA-LiPA25 assay. Oral HPV persistence for individual and grouped high-risk HPV types among 184 men positive for any high-risk HPV at their oral baseline visit was assessed at 6-month intervals. Factors associated with grouped high-risk HPV and HPV16 persistence were examined using logistic regression. Kaplan-Meier curves were constructed to examine median time to HPV clearance overall, and by selected risk factors.
Among the 7 HPV vaccine types, HPV33 had the longest median duration (7.6 months) followed by HPV16 and HPV45 (6.4 months). 10-30% of oral high-risk HPV inrstand the progression of oral HPV infection to HPV-OPC.Radiotherapy may synergize with programmed cell death 1 (PD1)/PD1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high-grade gliomas (HGGs).
Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W.
Thirty-two patients were enrolled (bevacizumab-naïve, n = 24; bevacizumab-resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab-naïve cohort, 20 patients (83%) had a complete response or partial response. The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI 9.46-18.46) and 7.92 months (95% CI 6.31-12.45), respectively. In the bevacizumab-resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI 8.97-18.86) with a median PFS of 6.54 months (95% CI 5.95-18.86). https://www.selleckchem.com/products/tauroursodeoxycholic-acid.html The majority of patients (n = 20/26; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression &lt;1%.
The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.
The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.